ارزیابی اثر سیموستاتین بر فعالیت آنزیم نیتریک اکساید سنتاز در رده سلولی اندوتلیال عروقی (HUVEC)

نوع مقاله : مقاله پژوهشی

نویسندگان

1 گروه داروسازی و علوم دارویی، واحد علوم ‌پزشکی تهران، دانشگاه آزاد اسلامی، تهران، ایران

2 گروه فیزیولوژی، واحد همدان، دانشگاه آزاد اسلامی، همدان، ایران

چکیده

سیموستاتین دارویی است که در کاهش سطح کلسترول کاربرد وسیعی دارد. با توجه به نقش گسترده NO در سیستم­های بیولوژیک بدن، می­توان از آن به عنوان یکی از اهداف درمانی در بیماری­های مختلف استفاده کرد. هدف از این پژوهش ارزیابی اثر سیموستاتین بر فعالیت آنزیم نیتریک اکسایدسنتاز در رده سلولی اندوتلیال عروقی HUVEC است. به منظور بررسی اثر سیمواستاتین بر رده سلولی HUVEC از روش MTT استفاده شد. اثر سیمواستاتین بر بیان ژن iNOS با استفاده از تکنیک Real-time PCR بررسی شد. تاثیر سیموستاتین بر سطح نیتریک اکساید در رده  سلولی آندوتلیال عروقی (HUVEC) با استفاده از رنگ‌سنجی گریس بررسی شد. بیان ژن آنزیم INOS در گروه دریافت کننده غلظت 55 میکرولیتر در میلی­لیتر سیمواستاتین، در مقایسه با گروه کنترل تفاوت معناداری داشت و افزایش یافت (05/0 P≤). سطح نیتریک اکساید در غلظت‌های بالاتر از 125 میکرولیتر بر میلی­لیتر سیموستاتین در مقایسه با گروه کنترل تفاوت معناداری نداشت. ولی در غلظت‌های پایین‌تر (16، 31 و 62 میکرولیتر بر میلی­لیتر) در مقایسه با گروه کنترل تفاوت معناداری مشاهده شد و افزایش یافت (05/0P≤). با توجه به ارتباط سطح آنزیم نیتریک اکساید سنتاز اندوتلیالی و اثرات آن بر به ویژه بیماری‌های قلبی- عروقی، و با توجه به تاثیر سیموستاتین بر افزایش بیان ژن نیتریک اکسابد سنتاز و سطح نیتریک اکساید استفاده از داروی سیموستاتین در بیمارانی که به خاطر اختلال در فعالیت نیتریک اکساید در سطح اندوتلیوم در معرض بیماری قرار می­گیرند ممکن است سودمند باشد.

کلیدواژه‌ها


عنوان مقاله [English]

The Effect Of Simvastatin On Nitric oxide Synthase Activity In Vascular Endothelial Cell Line (HUVEC)

نویسندگان [English]

  • Seyede Fatemeh Hosseini 1
  • Tahereh Naji 1
  • Rahim Ahmadi 2
1 Department of Pharmacy and Pharmaceutical Sciences, Tehran Medical Branch, Islamic Azad University, Tehran, Iran
2 Department of Physiology, Hamadan Branch, Islamic Azad University, Hamadan, Iran
چکیده [English]

Simvastatin is a 3-hydroxy-3-methylglutaryl coenzyme-A Reductase inhibitor widely used in lowering cholesterol levels.This study was aimed at assessing the effect of simvastatin on the activity of nitric oxide synthase in the vascular endothelial cell line HUVEC. MTT method was used to evaluate the effect of simvastatin on HUVEC vascular endothelial cell line. The effect of simvastatin on iNOS gene expression in HUVEC vascular endothelial cell line was investigated using real-time PCR technique. The effect of Simvastatin on the activity of endothelial nitric oxide synthase was investigated using grease colorimetry. With increasing Simvastatin concentration, the survival of HUVEC vascular endothelial cells decreased compared to the control group (P≤0.05). In addition, the expression of INOS enzyme gene in the group receiving 55 µl/ml of simvastatin was significantly different and increased compared to the control group (P≤0.05). Simvastatin at concentrations higher than 125 µl/ml simvastatin was not significantly different from the control group. However, at lower concentrations (62, 31, and 16 µl/ml), a significant difference was observed and increased compared to the control group (P≤0.05). Considering the decrease in the level of endothelial nitric oxide synthase and its effects on human diseases, especially cardiovascular diseases, the use of simvastatin can be helpful in patients exposed to disease due to endothelial nitric oxide dysfunction.
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کلیدواژه‌ها [English]

  • Simvastatin
  • Nitric Oxide Synthase Enzyme
  • HUVEC (Vascular Endothelial Cell
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